The expression of terminal deoxynucleotidyl transferase and paired box gene 5 in Merkel cell carcinomas and its relation to the presence of Merkel cell polyomavirus DNA

Johansson, Benjamin; Sahi, Helka; Koljonen, Virve; Böhling, Tom

doi:10.1111/cup.13372

Cited by 13 publications

(7 citation statements)

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“…In addition, the coexpression of terminal deoxy nucleotidyl transferase (TdT), paired box 5 (Pax5) and immunoglobulin chains, all markers expressed during B-cell differentiation, has been observed in MCC tumors (62, 64). Initially, the frequency of TdT and Pax5 positivity was reported to be about 65% ( N = 187) and 90% ( N = 143) of MCC cases (64); however, recently observed rates were lower, 26% ( N = 217) or 23% ( N = 213) (15, 63). Of note, expression of immunoglobulin chains was restricted to the MCPyV(+) subset and detected in about 70% of cases (65).…”

Section: Introductionmentioning

confidence: 99%

Histogenesis of Merkel Cell Carcinoma: A Comprehensive Review

et al. 2019

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Merkel cell carcinoma (MCC) is a primary neuroendocrine carcinoma of the skin. This neoplasia features aggressive behavior, resulting in a 5-year overall survival rate of 40%. In 2008, Feng et al. identified Merkel cell polyomavirus (MCPyV) integration into the host genome as the main event leading to MCC oncogenesis. However, despite identification of this crucial viral oncogenic trigger, the nature of the cell in which MCC oncogenesis occurs is actually unknown. In fact, several hypotheses have been proposed. Despite the large similarity in phenotype features between MCC tumor cells and physiological Merkel cells (MCs), a specialized subpopulation of the epidermis acting as mechanoreceptor of the skin, several points argue against the hypothesis that MCC derives directly from MCs. Alternatively, MCPyV integration could occur in another cell type and induce acquisition of an MC-like phenotype. Accordingly, an epithelial as well as a fibroblastic or B-cell origin of MCC has been proposed mainly based on phenotype similarities shared by MCC and these potential ancestries. The aim of this present review is to provide a comprehensive review of the current knowledge of the histogenesis of MCC.

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Section: Introductionmentioning

confidence: 99%

Histogenesis of Merkel Cell Carcinoma: A Comprehensive Review

et al. 2019

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“…In 2013, it was first proposed by zur Hausen and colleagues that pre/pro B cells are the origin cell of MCC, given that MCC expresses both terminal deoxynucleotidyl transferase (TdT) and paired box protein 5 (PAX5, the coexpression of which is only normally seen in B cells) and immunoglobulin [ 96 ]. Subsequent studies confirmed that the presence of B cell markers is positively correlated with MCPyV-positive status in MCC tumors [ 106 , 107 ]. The major questions underlying this hypothesis are whether MCPyV infects pre/pro B cells inside the dermis and whether these cells enter the dermis before or during oncogenesis.…”

Section: Cell Of Origin For MCCmentioning

confidence: 89%

Merkel cell polyomavirus and associated Merkel cell carcinoma

Yang

You

2022

Tumour Virus Research

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Merkel cell polyomavirus (MCPyV) is a ubiquitous skin infection that can cause Merkel cell carcinoma (MCC), a highly lethal form of skin cancer with a nearly 50% mortality rate. Since the discovery of MCPyV in 2008, great advances have been made to improve our understanding of how the viral encoded oncoproteins contribute to MCC oncogenesis. However, our knowledge of the MCPyV infectious life cycle and its oncogenic mechanisms are still incomplete. The incidence of MCC has tripled over the past two decades, but effective treatments are lacking. Only recently have there been major victories in combatting metastatic MCC with the application of PD-1 immune checkpoint blockade. Still, these immune-based therapies are not ideal for patients with a medical need to maintain systemic immune suppression. As such, a better understanding of MCPyV's oncogenic mechanisms is needed in order to develop more effective and targeted therapies against virus-associated MCC. In this review, we discuss current areas of interest for MCPyV and MCC research and the progress made in elucidating both the natural host of MCPyV infection and the cell of origin for MCC. We also highlight the remaining gaps in our knowledge on the transcriptional regulation of MCPyV, which may be key to understanding and targeting viral oncogenesis for developing future therapies.

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“…1,7 Besides, terminal deoxynucleotidyl transferase immuno-histo-staining can strengthen MCC diagnosis. 8 The recommended treatment for MCC is wide local excision with a healthy margin of 1-3 cm with adjacent therapies. Studies showed that MCC has a local recurrence, local lymph node metastasis, and distant metastasis rates of 20%-75%, 31%-80%, and 26%-75%, respectively.…”

Section: Discussionmentioning

confidence: 99%